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Engineered Living Intestinal Muscle Patch Produces Macroscopic Contractions that can Mix and Break down Artificial Intestinal Contents

The intestinal muscle layers execute various gut wall movements to achieve controlled propulsion and mixing of intestinal content. Engineering intestinal muscle layers with complex contractile function is critical for developing bioartificial intestinal tissue to treat patients with short bowel syndrome. Here we report the first demonstration of a living intestinal muscle patch capable of generating three distinct motility patterns and displaying multiple digesta manipulations. Assessment of cell contractility, cellular morphology, and transcriptome profile reveals that successful generation of the contracting intestinal muscle patch relies on both biological factors in a serum?free medium and environmental cues from an elastic electrospun gelatin scaffold. By comparing gene?expression patterns among samples, we show that biological factors from the medium strongly affect ion transport activities, while the scaffold unexpectedly regulates cell?cell communication. Analysis of the ligand?receptor interactome identifies the scaffold?driven changes in intercellular communication, and 78% of the upregulated ligand?receptor interactions are involved in the development and function of enteric neurons. Our discoveries highlight the importance of combining biomolecular and biomaterial approaches for tissue engineering. The living intestinal muscle patch represents a pivotal advancement for building functional replacement intestinal tissue. It offers a more physiological model for studying GI motility and for preclinical drug discovery.This article is protected by copyright. All rights reserved

Publication date: 13/02/2023

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This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 870292.